Mesp1 controls the speed, polarity, and directionality of cardiovascular progenitor migration

Chiapparo, Giuseppe; Lin, Xionghui; Lescroart, Fabienne; Chabab, Samira; Paulissen, Catherine; Pitisci, Lorenzo; Bondue, Antoine; Blanpain, Cédric

doi:10.1083/jcb.201505082

Cited by 47 publications

(57 citation statements)

References 49 publications

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“…The heart rudiment develops from a single pair of blastomeres in the 64‐cell stage, together with several other body muscles . The descendants of these blastomeres express Mesp , which has an essential role in the speed of migration and the specification of multipotent cardiac progenitor cells . In ascidians, Mesp1/2 is regulated by beta‐catenin, Tbx6 , and others.…”

Section: Cardiac Precursorsmentioning

confidence: 99%

“…10,14 The descendants of these blastomeres express Mesp, which has an essential role in the speed of migration and the specification of multipotent cardiac progenitor cells. 15 In ascidians, Mesp1/2 is regulated by beta-catenin, Tbx6, and others. Mesp1, likely representing the first element of the cardiac tool kit ( Figure 2), probably functions as a dual regulator, activating Ets1/2 and Hand-like and repressing Raldh2.…”

Section: Cardiac Precursorsmentioning

confidence: 99%

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Development and evolution of the metazoan heart

Poelmann

Groot

2019

Developmental Dynamics

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The mechanisms of the evolution and development of the heart in metazoans are highlighted, starting with the evolutionary origin of the contractile cell, supposedly the precursor of cardiomyocytes. The last eukaryotic common ancestor is likely a combination of several cellular organisms containing their specific metabolic pathways and genetic signaling networks. During evolution, these tool kits diversified. Shared parts of these conserved tool kits act in the development and functioning of pumping hearts and open or closed circulations in such diverse species as arthropods, mollusks, and chordates. The genetic tool kits became more complex by gene duplications, addition of epigenetic modifications, influence of environmental factors, incorporation of viral genomes, cardiac changes necessitated by air‐breathing, and many others. We evaluate mechanisms involved in mollusks in the formation of three separate hearts and in arthropods in the formation of a tubular heart. A tubular heart is also present in embryonic stages of chordates, providing the septated four‐chambered heart, in birds and mammals passing through stages with first and second heart fields. The four‐chambered heart permits the formation of high‐pressure systemic and low‐pressure pulmonary circulation in birds and mammals, allowing for high metabolic rates and maintenance of body temperature. Crocodiles also have a (nearly) separated circulation, but their resting temperature conforms with the environment. We argue that endothermic ancestors lost the capacity to elevate their body temperature during evolution, resulting in ectothermic modern crocodilians. Finally, a clinically relevant paragraph reviews the occurrence of congenital cardiac malformations in humans as derailments of signaling pathways during embryonic development.

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Section: Cardiac Precursorsmentioning

confidence: 99%

Section: Cardiac Precursorsmentioning

confidence: 99%

Development and evolution of the metazoan heart

Poelmann

Groot

2019

Developmental Dynamics

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“…Basic helix-loop-helix (bHLH) transcription factors Mesp1 and Mesp2 (Saga et al 2000) under the control of T-box factor Eomes (Costello et al 2011) regulate at least part of this process in mesoderm cells by directing the expression of genes involved in cardiac specification (Hand2, Gata4, Nkx2.5, and Myocd) and cellular migration (Prickle1 and RasGRP3) while actively repressing genes regulating pluripotency (Oct4, Nanog, and Sox2) and early mesoderm (T) and endoderm (Foxa2 and Sox17) fates (Bondue et al 2008;Costello et al 2011;Chiapparo et al 2016). Although these observations suggest that Mesp1/2 genes could act as master regulators of multipotent cardiovascular specification, retrospective lineage analysis (Saga et al 2000;Yoshida et al 2008) and in vitro differentiation studies (Chan et al 2013) have shown that Mesp1-expressing cells also contribute to a wide range of noncardiac derivatives, including hematopoietic precursors, skeletal muscle cells, and head mesenchyme.…”

mentioning

confidence: 99%

Id genes are essential for early heart formation

Cunningham

McKeithan

et al. 2017

Genes Dev.

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Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix-loop-helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation-Tcf3 and Foxa2-and activating inducers Evx1, Grrp1, and Mesp1. Most importantly, CRISPR/Cas9-mediated ablation of the entire Id (Id1-4) family in mouse embryos leads to failure of anterior cardiac progenitor specification and the development of heartless embryos. Thus, Id proteins play a central and evolutionarily conserved role during heart formation and provide a novel means to efficiently produce cardiovascular progenitors for regenerative medicine and drug discovery applications.[Keywords: cardiac progenitors; cardiac mesoderm specification; heartless; Id proteins; CRISPR/Cas9-mediated quadruple knockout; platform for cardiac disease modeling and drug discovery] Supplemental material is available for this article.

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“…During developmental processes and cancer progression, PRICKLE1 is required for oriented cell migration 2, 9, 11, 37 . At the molecular level, we and others have shown that PRICKLE1 contributes to localize VANGL at the plasma membrane 8, 12 , LL5β at the +ends of the microtubules 11 , and to restrict localization of the Rho-GAP at the edge of the migrating cancer cells 10 .…”

Section: Discussionmentioning

confidence: 99%

ECT2 associated to PRICKLE1 are poor-prognosis markers in triple-negative breast cancer

Daulat

Finetti

Revinski

et al. 2018

Preprint

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BackgroundTriple-negative breast cancers are poor-prognosis tumors characterized by absence of molecular signature and are chemotherapy is still the only systemic treatment. Currently, research focus to identify biomarkers that may be usable for prognosis and/or for treatment, notably among the proteins involved in cell migration and metastatic capacity.MethodsWe used proteomic approach to identify protein complexes associated to PRICKLE1 and the mRNA expression level of the corresponding genes in a retrospective series of 8,982 clinically annotated patients with invasive primary breast cancer were assessed. Then, we characterize molecularly the interaction between PRICKLE1 and the guanine nucleotide exchange factor ECT2. Finally, experiments in Xenopus have been carrying out to determine their evolutionary conserved interaction.ResultsWe have identified a network of proteins interacting with the prometastatic scaffold protein PRICKLE1 that includes several small G-protein regulators involved in cell migration and metastasis. Combined analysis expression of PRICKLE1 and small G-protein regulators expression has a strong prognostic value in TNBC. We show that PRICKLE1 controls the activity of ECT2 on RAC1 signaling, a pathway required for cancer cell dissemination.ConclusionsThis work supports the idea that promigratory proteins, which are overexpressed in cancerous epithelium, are suitable pharmaceutical targets.

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Mesp1 controls the speed, polarity, and directionality of cardiovascular progenitor migration

Cited by 47 publications

References 49 publications

Development and evolution of the metazoan heart

Development and evolution of the metazoan heart

Id genes are essential for early heart formation

ECT2 associated to PRICKLE1 are poor-prognosis markers in triple-negative breast cancer

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